Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-02-01 DOI:10.22074/cellj.2024.2016937.1459

Yusef Abbasi, Marziyeh Pooladi, Roya Nazmabadi, Jamal Amri, Helia Abbasi, Hadi Karami

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引用次数: 0

Abstract

Objective: Enhanced cell survival and drug resistance in tumor cells have been linked to the overexpression of antiapoptotic members of the Bcl-2 family proteins, including Bcl-2 and Mcl-1. The aim of this study was to explore the impact of formononetin and dihydroartemisinin combination on the growth and apoptosis of acute myeloid leukemia (AML) cells.

Materials and methods: In this experimental study, the cell survival and cell proliferation were tested by MTT assay and trypan blue staining. The evaluation of cell apoptosis was conducted using Hoechst 33342 staining and a colorimetric assay to measure caspase-3 activity. To determine the mRNA levels of Mcl-1, Bcl-2, Bax, and Cyclin D1, a quantitative real-time polymerase chain reaction (qRT-PCR) was performed.

Results: We showed that treatment with either formononetin or dihydroartemisinin alone, led to significant decrease in the cell survival and growth, and triggered apoptosis in U937 and KG-1 AML cell lines. Moreover, treatment with each of the compounds alone significantly decreased the mRNA levels of Mcl-1, Bcl-2 and Cyclin D1 mRNA, while, the expression level of Bax mRNA was enhanced. Combination of two compounds showed a synergistic anti-cancer effect.

Conclusion: The anti-leukemic potential of formononetin and dihydroartemisinin is exerted through the effect on cell cycle progression and intrinsic pathway of apoptosis. Therefore, they can be considered as a potential anti-leukemic agent alone or along with existing chemotherapeutic drugs.

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福莫西汀和双氢青蒿素协同诱导人类急性髓性白血病细胞株凋亡

目的：肿瘤细胞存活率和耐药性的增强与Bcl-2家族蛋白（包括Bcl-2和Mcl-1）等抗凋亡成员的过度表达有关。本研究旨在探讨甲萘素和双氢青蒿素复方制剂对急性髓性白血病（AML）细胞生长和凋亡的影响：在本实验研究中，细胞存活率和细胞增殖率通过 MTT 试验和胰蓝染色进行检测。细胞凋亡的评估采用 Hoechst 33342 染色法和比色法测量 caspase-3 活性。为了确定 Mcl-1、Bcl-2、Bax 和 Cyclin D1 的 mRNA 水平，进行了实时定量聚合酶链反应（qRT-PCR）：结果表明，单独使用甲萘素或双氢青蒿素处理 U937 和 KG-1 AML 细胞系，可显著降低细胞存活率和生长率，并引发细胞凋亡。此外，单独使用这两种化合物会明显降低 Mcl-1、Bcl-2 和 Cyclin D1 mRNA 的表达水平，同时提高 Bax mRNA 的表达水平。两种化合物的组合具有协同抗癌作用：结论：甲萘素和双氢青蒿素的抗白血病潜力是通过影响细胞周期进展和细胞凋亡的内在途径而发挥的。因此，它们可被视为一种潜在的抗白血病药物，既可单独使用，也可与现有的化疗药物一起使用。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.